The frequent occurrence of pneumonitis and pulmonary fibrosis secondary to radiation therapy and/or chemotherapy in combined modality cancer treatment has led to search for a predictive index. The morbidity and mortality after the onset of a diffuse pneumonitis or fibrosis is high and recognition of this entity in the pre-clinical phase may allow for interventions to avoid its onset. Toward this end, we have pursued studies on Type II pneumocyte as a beginning point to understand radiation pneumonitis. The Type II pneumocyte has been shown to be an early target of radiation and releases surfactant into alveoli shortly after exposure. By use of lavaging techniques, alveolar surfactant has been shown to be elevated after pulmonary irradiation. Pulmonary lethalith occurred four months later in LAF, mice, indicating a strong correlation with surfactant release at 7 and 28 days. For this reason, further experiments are proposed to refine the acute biochemical alterations of Type II pneumocytes as a predictor for later effects. When these changes are identified in in vitro and in vivo studies on mice, they will be studied as markers in larger animal diagnostic models (rabbits and dogs) prior to their introduction in man. The causal relationship between radiation effects on Type II pneumocytes, other pulmonary cells and pneumonitis and fibrosis, will be evaluated in a variety of correlated biochemical, histological and ultrastructural techniques. Studies on modification of radiation response by different radiation fractionation schema and to chemotherapeutic and radioprotective agents will also be under study. Surfactant, its precursors on other changes in Type II pneumocytes has the potential for being the first early biochemical marker for late radiation effects.